Development of an emulgel for the treatment of rosacea using quality by design approach.

Objective: The aim of this study was to develop an emulgel for the treatment of rosacea, applying quality by design (QbD).Methods: An emulgel designed to release the active pharmaceutical ingredients (APIs), metronidazole and niacinamide, via an emollient formulation that favors residence time and attenuates facial redness would be an excellent vehicle to develop to treat rosacea. It was decided to design first a vehicle presenting the attributes established in the quality target product profile, and then, after selecting the best formulation, to load the APIs in it to optimize the final emulgel. A design of experiments was introduced to study the effect of formulation variables on quality attributes (adhesion, phase separation by mechanical stress and viscosity) of the emulgels. Response surface methodology and desirability functions were applied for data analysis. After optimization, the final emulgel was further characterized by assay and in vitro release of APIs, attenuation of facial redness, and compared to commercially available metronidazole products regarding API release.Results: The final emulgel gradually released both APIs, reaching approximately 88% within the first 4 h, and their profiles were well described by the Higuchi model. Only a light attenuation effect to conceal facial redness was achieved.Conclusions: A metronidazole and niacinamide emulgel, also providing cosmetic assistance, was developed using QbD. The emulgel releases metronidazole faster than the creams, but more gradually than the commercially available gel, providing a realistic time frame of drug delivery in accordance with the expected time of residence of the adhesive emulgel over the affected facial area.

Study of the Influence of Formulation Variables in Bioadhesive Emulgels Using Response Surface Methodology.

The aim of the present work was to study the main formulation variables that influence attributes of bioadhesive emulgels based on a combination of polymers, using response surface methodology (RSM). Bioadhesive products continue to gain attention in topical cutaneous administration as they allow long residence times on the application site, which is important when a long dermal action and a reduced product administration frequency are desired. A Box-Behnken design of experiments (DoE) was introduced to study the effect of formulation variables on quality attributes of the emulgels. The effects of concentration of carbomer interpolymer type A (Polym1), xanthan gum (Polym2) and mineral oil (Oil) on detachment force (Fdetch), spreadability (Spread), and phase separation by mechanical stress (PhSep) were investigated. RSM and desirability functions were applied for data analysis. Emulgels were further characterized by viscosity and extrudability measurements. Polym1 showed a positive effect on Fdetch, while the increase in concentrations of Polym2 and Oil decreased this property. Polym1 and Polym2 favored emulgel PhSep. However, their interaction effect decreased it. The combination of 0.4-0.6% of carbomer and 0.2-0.3% of gum was able to produce easy-to-spread bioadhesive emulgels with mineral oil as discontinuous phase in the presence of a low surfactant concentration. Based on the DoE results, value ranges for the variables, which could achieve for the experimental domain to get the critical quality attributes of emulgels jointly within the specification limits, were able to be identified using RSM supported by desirability functions.

Application of multivariate techniques in the evaluation of melt granulation products

In this work, principal component analysis and cluster analysis were applied as helping tools to extract useful information in the development of formulations and manufacturing processes of melt granulates. Two melt granulation processes that differ in the shear stress applied to the solid bed during melting step were designed. These processes employ equipment frequently used in the local pharmaceutical industry. The selected binders include both hydrophilic and hydrophobic excipients, which were used alone or in binary mixtures. Granulates were characterized regarding their physicomechanical properties, including their compaction behavior. The resulting tablets were also evaluated. The selected multivariate statistical methods proved to be useful in facilitating the interpretation of the collected data and the study of the properties of granulates and tablets, as well as the selection of more efficient production processes.

Neste trabalho, foram aplicadas as técnicas de análise de componentes principais e de análise de agrupamentos para extrair informações úteis no desenvolvimento de formulações e de processos de produção de granulados por fusão. Desenharam-se dois processos de granulação por fusão que apresentam diferenças na tensão de cisalhamento aplicada ao leito sólido durante a etapa de fusão. Esses processos empregam equipamentos frequentemente usados na indústria farmacêutica local. Os ligantes escolhidos incluíram excipientes tanto hidrofílicos quanto hidrofóbicos, utilizados de forma individual ou em misturas binárias. Os granulados foram caracterizados quanto às suas propriedades físico-mecânicas, incluindo seu desempenho no processo de compactação. Os comprimidos resultantes também foram avaliados. Os métodos de análise multivariada escolhidos provaram ser úteis para facilitar a interpretação dos dados coletados e o estudo das propriedades dos granulados e dos comprimidos, bem como a seleção de processos de produção mais eficientes.